Various types of tests related to patient diagnosis and therapy can be performed by analysis assays of a sample of a patient's infections, bodily fluids or abscesses. Such patient samples are typically placed in sample vials, extracted from the vials, combined with various reagents in special reaction vessels or tubes, incubated, and analyzed to aid in treatment of the patient. In typical clinical chemical analyses, one or two assay reagents are added at separate times to a liquid sample having a known concentration, the sample-reagent combination is mixed and incubated. Interrogating measurements, turbidimetric or fluorometric or absorption readings or the like are made to ascertain end-point or rate values from which an amount of analyte may be determined, using well-known calibration techniques.
Although various known clinical analyzers for chemical, immunochemical and biological testing of samples are available, analytical clinical technology is challenged by increasing needs for improved levels of analysis. Automated clinical analyzers improve operating efficiency by providing results more rapidly while minimizing operator or technician error. However, due to increasing demands on clinical laboratories regarding assay throughput, new assays for additional analytes, accuracy of analytical results, and low reagent consumption, there continues to be a need for improvements in the overall performance of automated clinical analyzers. In particular, sample analysis continuously needs to be more cost effective in terms of reduced testing turnaround time which is usually addressed by increasing analyzer throughput, regardless of the assay to be performed.
An important contributor to maintaining a high throughput of automatic analyzers is the ability to quickly process a plurality of samples through a variety of different assay process and signal measurement steps. If there were no premium placed on space within health care facilities, automatic clinical analyzers could be designed for high-speed throughput and reliability by simply spacing apart multiple numbers of rugged components in dedicated positions to carry out different assay technologies. This is not feasible and even further, there are different standards for evaluating the rate of throughput of an automatic clinical analyzer. A volume throughput measurement relates to how much time is required for all assays on all samples to be tested to be completed. Conversely, an assay throughput measurement relates to how much time is required for a specified assay of a specified sample to be completed. For example, in terms of volume throughput, 1000 patient samples may be completed during 4 hours but the first result may be available only 3 hours after start-up. However, in terms of assay throughput, a first assay result may be available 30 minutes after a sample is placed on an analyzer but the last result may be available only 10 hours after start-up. Such diverse throughput's are not generally acceptable to laboratory personnel and therefore automatic analyzers are required to simultaneously have a high volume processing throughput in terms of sample assays/hour as well as a fast turn-around time to the first available reportable result.
One common method of scheduling assay resources to maximize throughput is based upon the use of a predetermined fixed cycle where all assay resources in the instrument operate within a fixed length, predetermined cycle. Systems having this scheduling method have each assay resource returning to a predetermined location at the end of each cycle. Automated analyzers which use a predetermined fixed cycle method of scheduling the timing of resources also have single chronology operation. Each container of sample proceeds through each of the operational stations of the analyzer in the same order. The Stratus® II Immunoassay System is such an automated immunoassay system and is described in Volume 41 of the I. Clin. Immun. In the Stratus analyzer, a generally circular reaction carousel moves forward a fixed distance for each cycle of the system, indexing sequentially in a clockwise fashion past an incubation stage, a washing stage and a reading stage. A similar process is described in U.S. Pat. No. 5,575,976 in which each assay resource has a predetermined fixed operation window within the fixed processing cycle. Resultingly, the control for one assay resource can rely on predetermined timing of other dependent and independent assay resources. Therefore, analyte tests having variable protocols and that are processed by moving reaction vessels in different chronologies can be interleaved if their assay resource requirements do not conflict, i.e., analyte tests with shorter processing time can be entered after those with longer processing times and the shorter analyte test can finish first. This can be achieved because the means of transporting reaction vessels containing assay constituents can present reaction vessels to the necessary assay resources in whatever order is required, regardless of entry order.
U.S. Pat. No. 5,434,083 uses a rotating reaction vessel train in which an analysis time of each of the test items is set to correspond to the number of times of circulation (number of cycles) of the reaction vessels on the reaction line. A reaction vessel renew device is selectively controlled for each reaction vessel in accordance with the number of cycles. Thus, a test item which requires a short reaction time is processed in a smaller number of cycles of the reaction line and a test item which requires a long reaction time is processed in a larger number of cycles The analyzer can sequentially process a plurality of test items which require different reaction times for one sample.
U.S. Pat. No. 5,482,861 operates an automated continuous and random access analytical system capable of simultaneously effecting multiple assays of a plurality of liquid samples wherein scheduling of various assays of the plurality of liquid samples is followed by creating a unit dose and separately transferring a first liquid sample and reagents to a reaction vessel without initiation of an assay reaction sequence, followed by physical transfer of the unit dose disposable to a processing workstation, whereby a mixture of the unit dose disposable reagents and sample are achieved during incubation.
U.S. Pat. No. 5,576,215 operates a biological analyzer wherein instrument systems used to perform assays of the biological samples loaded into the analyzer are operated in accordance with a schedule developed by a scheduler routine. The scheduler routine determines interval periods between operations performed by the analyzer instrument systems on each biological sample as a function of an entered load list unless a fixed interval period between the operations is required and schedules instrument system operations and the determined interval periods. The biological system analyzer performs assays of the biological samples by operating the analyzer instrument systems in accordance with the developed schedule.
U.S. Pat. No. 5,679,309 discloses a method for controlling an analyzer including a rotatable, circular reaction carousel which has circumferentially spaced cuvettes. Each cuvette, according to the menu of the analyzer, is designated to receive a selected reagent and a selected sample for reaction and analysis and, post-analysis, be washed for re-use. A drive indexes the reaction carousel to position the cuvettes according to the menu and in proper sequence, for receipt of reagent, sample and for wash and for analysis. When photometric analysis is used, the drive operates on a sequence of a spin cycle, during which the reaction carousel is spun for photometric analysis of reacting cuvettes, and a park cycle, for a period of time for insertion of reactant, sample and/or for wash.
U.S. Pat. No. 5,846,491 increases throughput by employing an analyzer control system with means for allocating assay resources to one of a number of reaction vessels as a function of the time cycle for that vessel and transferring reaction vessels directly from one assay resource station to another according to a chronology selected from a plurality of different predetermined chronologies.
U.S. Pat. No. 5,985,672 also addresses the need for high-speed processing by employing a pre-processor for use in performing immunoassays on samples for analytes in the sample employing concentrically positioned incubating and processing carousels. A single transfer station permits reaction vessels containing sample and reagents to be moved between the carousels. The samples are separated, washed and mixed on the processing carousel and incubated on the incubating carousel thus speeding up processing throughput.
Another scheduling method used in automated analyzers does not use a fixed cycle, instead using a scheduling method referred to as “kitting.” U.S. Pat. No. 6,096,561 discloses an automated continuous and random access analytical system, capable of simultaneously effecting multiple assays of a plurality of liquid samples wherein various assays are scheduled for a plurality of liquid samples. Through kitting, the system is capable of creating a unit dose by separately transferring liquid sample and reagents to a reaction vessel without initiation of an assay reaction sequence. From the kitting means, multiple, kitted unit dose disposables are transferred to a process area, where an aliquot is mixed for each independent sample with one or more liquid reagents at different times in a reaction vessel to form independent reaction mixtures. Independent scheduling of kitting and mixing is achieved during incubation of the multiple reaction mixtures, simultaneously and independently. The system is capable of performing more than one scheduled assay in any order in which a plurality of scheduled assays is presented. The incubated reaction mixtures are analyzed independently and individually by at least two assay procedures which are previously scheduled.
From this discussion of the art state in automated clinical analyzers, it may be seen that while has been considerable progress has been made toward increasing processing efficiency, there remains an unmet need for a system and apparatus that provides a high volume throughput for unpredictable combinations of different type assays, particularly those which require various lengths of time to complete an assay including incubation and final reading and/or single and multiple reagent additions. There further remains an unmet need for a system and apparatus for efficiently completing unpredictable combinations of assays which require relatively longer and relatively shorter processing times.